Wednesday, October 21, 2009

What's new for 'Trypanosomatids' in PubMed

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Search kinetoplastids OR kinetoplastid OR Kinetoplastida OR "trypanosoma brucei" OR leishmania OR brucei OR leishmaniasis OR "African trypanosomiasis"
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PubMed Results
Items 1 -9 of 9

1: PLoS Negl Trop Dis. 2009 Oct 20;3(10):e536.

Inaccuracy of Enzyme-Linked Immunosorbent Assay Using Soluble and Recombinant Antigens to Detect Asymptomatic Infection by Leishmania infantum.

Moreno EC, Gonçalves AV, Chaves AV, Melo MN, Lambertucci JR, Andrade AS, Negrão-Corrêa D, de Figueiredo Antunes CM, Carneiro M.

Departamento de Parasitologia, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Programa de Pós-Graduação em Parasitologia, Belo Horizonte, Minas Gerais, Brasil.

BACKGROUND: One of the most important drawbacks in visceral leishmaniasis (VL) population studies is the difficulty of diagnosing asymptomatic carriers. The aim of this study, conducted in an urban area in the Southeast of Brazil, was to evaluate the performance of serology to identify asymptomatic VL infection in participants selected from a cohort with a two-year follow-up period. METHODOLOGY: Blood samples were collected in 2001 from 136 cohort participants (97 positive and 39 negatives, PCR/hybridization carried out in 1999). They were clinically evaluated and none had progressed to disease from their asymptomatic state. As controls, blood samples from 22 control individuals and 8 patients with kala-azar were collected. Two molecular biology techniques (reference tests) were performed: PCR with Leishmania-generic primer followed by hybridization using L. infantum probe, and PCR with specific primer to L. donovani complex. Plasma samples were tested by ELISA using three different antigens: L. infantum and L. amazonensis crude antigens, and rK39 recombinant protein. Accuracy of the serological tests was evaluated using sensitivity, specificity, likelihood ratio and ROC curve. FINDINGS: The presence of Leishmania was confirmed, by molecular techniques, in all kala-azar patients and in 117 (86%) of the 136 cohort participants. Kala-azar patients showed high reactivity in ELISAs, whereas asymptomatic individuals presented low reactivity against the antigens tested. When compared to molecular techniques, the L. amazonensis and L. infantum antigens showed higher sensitivity (49.6% and 41.0%, respectively) than rK39 (26.5%); however, the specificity of rK39 was higher (73.7%) than L. amazonensis (52.6%) and L. infantum antigens (36.8%). Moreover, there was low agreement among the different antigens used (kappa<0.10). CONCLUSIONS: Serological tests were inaccurate for diagnosing asymptomatic infections compared to molecular methods; this could lead to misclassification bias in population studies. Therefore, studies which have used serological assays to estimate prevalence, to evaluate intervention programs or to identify risk factors for Leishmania infection, may have had their results compromised.

PMID: 19841736 [PubMed - in process]

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2: Mar Drugs. 2009 Aug 11;7(3):361-6.

The Mediterranean Red Alga Asparagopsis: A Source of Compounds against Leishmania.

Genovese G, Tedone L, Hamann MT, Morabito M.

Department of Life Sciences "M. Malpighi"-Botany, University of Messina, Salita Sperone, 31, 98166 Messina, Italy; E-Mails: laura.tedone@gmail.com (L.T.); morabitom@unime.it (M.M.).

Crude extracts and column fractions from the red algae Asparagopsis taxiformis and A. armata from the Strait of Messina (Italy) were screened for the production of antimicrobial compounds. Extracts from both species revealed remarkable antiprotozoal activity against Leishmania, revealing such algae as a great source of natural antiprotozoal products.

PMID: 19841720 [PubMed - in process]

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3: J Biol Chem. 2009 Oct 19. [Epub ahead of print]

A single UDP-galactofuranose transporter is required for galactofuranosylation in aspergillus fumigatus.

Engel J, Schmalhorst PS, Dork-Bousset T, Ferrieres V, Routier FH.

Hannover Medical School, Germany;

Galactofuranose (Galf) containing molecules have been described at the cell surface of several eukaryotes and shown to contribute to the virulence of the parasite Leishmania major and the fungus Aspergillus fumigatus. It is anticipated that a number of the surface glycoconjugates such as N-glycans or glycolipids are galactofuranosylated in the Golgi apparatus. This raises the question how the substrate for galactofuranosylation reactions, UDP-Galf, which is synthesized in the cytosol, translocates into the organelles of the secretory pathway. Here we report the first identification of a Golgi localized nucleotide sugar transporter with specificity for UDP-Galf named GlfB. In vitro transport assays established binding of UDP-Galf to GlfB and excluded transport of several other nucleotide sugars. Furthermore, the implication of glfB in the galactofuranosylation of A. fumigatus glycoconjugates and galactomannan was demonstrated by a targeted gene deletion approach. Our data reveal a direct connection between galactomannan and the organelles of the secretory pathway which strongly suggests that the cell wall bound polysaccharide originates from its GPI-anchored form.

PMID: 19840949 [PubMed - as supplied by publisher]

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4: BMC Genomics. 2009 Oct 19;10(1):482. [Epub ahead of print]

Widespread variation in transcript abundance within and across developmental stages of Trypanosoma brucei.

Jensen BC, Sivam D, Kifer CT, Myler PJ, Parsons M.

ABSTRACT: BACKGROUND: Trypanosoma brucei, the causative agent of African sleeping sickness, undergoes a complex developmental cycle that takes place in mammalian and insect hosts and is accompanied by changes in metabolism and cellular morphology. While differences in mRNA expression have been described for many genes, genome-wide expression analyses have been largely lacking. Trypanosomatids represent a unique case in eukaryotes in that they transcribe protein-coding genes as large polycistronic units, and rarely regulate gene expression at the level of transcription initiation. RESULTS: Here we present a comprehensive analysis of mRNA expression in several stages of parasite development. Utilizing microarrays that have multiple copies of multiple probes for each gene, we were able to demonstrate with a high degree of statistical confidence that approximately one-fourth of genes show differences in mRNA expression levels in the stages examined. These include complex patterns of gene expression within gene families, including the large family of variant surface glycoproteins (VSGs) and their relatives, where we have identified a number of constitutively expressed family members. Furthermore, we were able to assess the relative abundance of all transcripts in each stage, identifying the genes that are either weakly or highly expressed. Very few genes show no evidence of expression. CONCLUSIONS: Despite the lack of gene regulation at the level of transcription initiation, our results reveal extensive regulation of mRNA abundance associated with different life cycle and growth stages. In addition, analysis of variant surface glycoprotein gene expression reveals a more complex picture than previously thought. These data provide a valuable resource to the community of researchers studying this lethal agent.

PMID: 19840382 [PubMed - as supplied by publisher]

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5: BMC Bioinformatics. 2009 Oct 19;10(1):344. [Epub ahead of print]

TIde: a software for the systematic scanning of drug targets in kinetic network models.

Schulz M, Bakker BM, Klipp E.

ABSTRACT: BACKGROUND: During the stages of the development of a potent drug candidate compounds can fail for several reasons. One of them, the efficacy of a candidate, can be estimated in silico if an appropriate ordinary differential equation model of the affected pathway is available. With such a model at hand it is also possible to detect reactions having a large effect on a certain variable such as a substance concentration. RESULTS: We show an algorithm that systematically tests the influence of activators and inhibitors of different type and strength acting at different positions in the network. The effect on a quantity to be selected (e.g. a steady state flux or concentration) is calculated. Moreover, combinations of two inhibitors or one inhibitor and one activator targeting different network positions are analysed. Furthermore, we present TIde (Target Identification), an open source, platform independent tool to investigate ordinary differential equation models in the common Systems Biology Markup Language format. It automatically assigns the respectively altered kinetics to the inhibited or activated reactions, performs the necessary calculations, and provides a graphical output of the analysis results. For illustration, TIde is used to detect optimal inhibitor positions in simple branched networks, a signalling pathway, and a well studied model of glycolysis in Trypanosoma brucei. CONCLUSIONS: Using TIde, we show in the branched models under which conditions inhibitions in a certain pathway can affect molecule concentrations in a different. In the signalling pathway we illuminate which inhibitions have an effect on the signalling characteristics of the last active kinase. Finally, we compare our set of best targets in the glycolysis model with a similar analysis showing the applicability of our tool.

PMID: 19840374 [PubMed - as supplied by publisher]

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6: Parasite. 2009 Sep;16(3):231-3.

Sandflies of the south part of Ouagadougou City, Burkina Faso.

Sangare I, Gantier JC, Koalaga G, Deniau M, Ouari A, Guiguemdé RT.

Service de Parasitologie-Mycologie, INSSA de Bobo-Dioulasso et Faculté de Médecine de Ouagadougou, Burkina Faso.

Since 1996, the number of cases of cutaneous leishmaniasis has increased dramatically in Ouagadougou. Leishmania major, zymodeme MON74 was the only strain isolated in this focus. An epidemiological study of the phlebotomine sandflies fauna has been undertaken. Collections of sandflies have been carried out in six areas of the town during one year with two intensive collections at the end of the dry (May-June) and wet seasons (September-October). The only species of genus Phlebotomus captured was P. duboscqi. This represented 11.2% from the 4,676 collected sandflies. P. duboscqi is a well known vector of L. major, nevertheless, none of the collected sandflies were infected with L. major. 16 species of Sergentomyia were present in the south area of Ouagadougou and S. schwetzi was the most abundant sandfly.

PMID: 19839270 [PubMed - in process]

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7: Parasite. 2009 Sep;16(3):227-30.

A combination DNA vaccine encoding nucleoside hydrolase 36 and glycoproteine 63 protects female but not male hamsters against Leishmania mexicana.

Chalé-Balboa WG, Mut-Martin M, Ramirez-Sierra MJ, Garcia-Miss MR, Dumonteil E.

Laboratorio de Parasitología, Centro de Investigaciones Regionales "Dr. Hideyo Noguchi", Universidad Autónoma de Yucatán, Mérida, Yucatán, México.

Leishmaniasis is a group of diseases caused by protozoan parasites of the Leishmania genus. Previous studies have shown that a DNA vaccine encoding Leishmania donovani antigen nucleoside hydrolase 36 and L. mexicana glycoprotein 63 is protective in mice. We investigated here the efficacy of this DNA vaccine to induce protection in golden hamsters. Male hamsters were more susceptible to infection by Leishmania mexicana than females. Following immunization with two doses of the DNA vaccine, only females resulted protected while males developed normal lesions.

PMID: 19839269 [PubMed - in process]

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8: Parasite. 2009 Sep;16(3):215-21.

Study of the stress proteins secreted by Leishmania donovani after treatment with edelfosine, mitelfosine and ilmofosine, and morphological alterations analyzed by electronic microscopy.

Azzouz S, Maache M, Sarciron ME, Petavy AF, Osuna A.

Département de Parasitologie et Mycologie médicale, Université Claude Bernard - Lyon I, 8, av. Rockefeller, 69373 Lyon Cedex 08, France. sazzouz@ugr.es

We studied the stress proteins induced in protozoa Leishmania donovani after treatment with edelfosine, miltefosine and ilmofosine. We studied the morphological and structural modifications caused in the promastigote forms of the parasite after treatment with the three alkyl-lysophospholipids (ALPs). A resistant strain of L. donovani to miltefosine was obtained and the morphological modifications were observed. The stress proteins induction was studied in promastigote forms and also in amastigote-like forms obtained in vitro. The proteins synthesized with the three alkyl-lysophospholipids were compared to those obtained by heat shock. The axenic amastigote forms synthesized a pattern of different proteins for those observed in the promastigote forms. The morphological alterations were observed under electronic microscopy. The membrane and mitochondria were the organs most affected by the three ALPs. We noted an apparition of vacuoles and vesicles in the treated promastigotes. In the resistant strain, we noted myelin bodies in the treated and untreated parasites.

PMID: 19839267 [PubMed - in process]

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9: Parasitol Res. 2009 Oct;105(4):1031-9. Epub 2009 Jun 10.Click here to read LinkOut

Expression of cytokines and chemokines and microvasculature alterations of the tongue from patients with chronic Chagas' disease.

de Lima Pereira SA, Severino VO, Kohl NL, Rodrigues DB, Alves PM, Clemente-Napimoga JT, dos Reis MA, Teixeira VP, Napimoga MH.

Laboratory of Biopathology and Molecular Biology, University of Uberaba, Av. Nenê Sabino, 1801, Bairro Universitário, Uberaba CEP 38.055-500, Minas Gerais, Brazil. sanivia.pereira@uniube.br

Chagas' disease is caused by the protozoan Trypanosoma cruzi and continues to be a significant public health problem, since 10 million people are still infected in Latin America. The purpose of this study was to analyze the microvasculature alterations as well the expression of cytokines and chemokines in the tongues from patients with chronic Chagas' disease (CC; n = 18), comparatively with a non-chagasic group (NC; n = 22). We observed several vascular alterations in the tongue of CC such as a greater vascular diameter, increased vascular wall area, high density of the blood vessels, and increased thickening of the capillary basement membrane. The expression of cytokines interferon gamma and tumor necrosis factor alpha and chemokine macrophage inflammatory protein 1alpha were significantly down-regulated in the tongue of CC group. These results demonstrated that, in the tongue of chagasic patients, a microvascular abnormality and immunological impairment occurs, probably due to chronic inflammation evoked by T. cruzi antigens.

PMID: 19513749 [PubMed - indexed for MEDLINE]

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